Daily orforglipron treatment reduces weight and blood sugar in seniors

In continuation of my update on orforglipron

A new analysis to be presented at this year's European Congress on Obesity (ECO 2026, Istanbul, Turkey, 12-15 May) examined daily oral orforglipron treatment for the treatment of obesity, with or without diabetes, in users aged 65 years and over, with results and a safety profile similar to that seen in the ATTAIN clinical trial programme population. Lead author for this post-hoc analysis is Dr Deborah Horn, Director of the Center for Obesity Medicine and Metabolic Performance at McGovern Medical School at UTHealth Houston, Houston, Texas, USA, and colleagues.

Limited clinical data exist on the use of incretin-based obesity management medications in older adults with or without type 2 diabetes (T2D), and a lack of specific analyses related to older users could be a factor that could make providers or patients in this age group hesitant when considering therapy choices.

Orforglipron is a novel small-molecule, non-peptide, oral glucagon-like peptide-1 receptor agonist (GLP-1 RA) developed by Eli-Lilly and Company (Lilly), who sponsored these analyses. The drug was approved by the US Food and Drug Administration for chronic weight management on April 1, 2026.

Orforglipron demonstrated significant weight reduction vs. placebo in the phase 3, randomised, double-blind, multinational ATTAIN-1 and ATTAIN-2 clinical trials in participants with obesity or obesity and T2D, respectively. In this new analysis of those trials, the authors evaluated efficacy and safety of orforglipron versus placebo in a sub-group of participants aged 65 years and older from ATTAIN-1 and ATTAIN-2.

The ATTAIN-1 and ATTAIN-2 global clinical trials evaluated once-daily orforglipron 6 mg, 12 mg, or 36 mg vs. placebo as an adjunct to healthy diet and physical activity in participants from 9 and 10 countries, respectively. In this sub-group analysis, efficacy outcomes were analysed separately for each trial, and safety data were pooled. The primary endpoint was percent change in body weight from baseline to week 72.

In ATTAIN-1 and ATTAIN-2, 616 randomised participants were ≥65 years of age (n=196 and 420, respectively). Of those, 613 received treatment (orforglipron 6 mg, n=118; 12 mg, n=135; 36 mg, n=146; placebo, n=214). And 79.1% of ATTAIN-1 and 86.2% of ATTAIN-2 participants had hypertension as a comorbidity.

At Week 72, the percent change in weight from baseline in users aged 65 and over in ATTAIN-1 (participants with obesity and without T2D) was –7.9%, –11.3%, and –13.0% with orforglipron 6 mg, 12 mg, and 36 mg, respectively, vs. –1.6% with placebo, all statistically significant findings. Similar results were found for those users aged 65 years and over with T2D and obesity in ATTAIN-2: orforglipron 6 mg: –7.5%; 12 mg: –8.3%; 36 mg: –12.2%; placebo: –2.3% again with all results statistically significant.

Participants with T2D experienced reductions from baseline in glycated haemoglobin (HbA1c – a measure of blood sugar control) of –1.5%, –1.6%, and –1.7% with 6 mg, 12 mg, and 36 mg orforglipron, respectively, vs. –0.1% with placebo. BMI, waist circumference, triglycerides, non-HDL cholesterol, and health-related quality of life also improved in orforglipron vs. placebo treatment groups in participants with or without T2D. 

https://en.wikipedia.org/wiki/Orforglipron

Daily orforglipron treatment reduces weight and blood sugar in seniors

Semaglutide shows sustained weight loss benefits in older adults

In continuation of my update on semaglutide

A new analysis of the STEP trails carried out by semaglutide manufacturer Novo Nordisk has analysed various trials to show the safety and efficacy of the obesity drug semaglutide in older adults (over 65 years), and found similar efficacy and safety as in the general trial populations . The study is by Prof Luca Busetto from the University of Padova in Italy and colleagues including from Novo Nordisk, who sponsor this new study.

Individuals of advanced age with obesity represent a vulnerable group, often presenting with comorbidities and frailty, and being at risk of adverse events (AEs). Information on the use of glucagon-like peptide-1 (GLP-1) receptor agonists including semaglutide in this population is limited; therefore, the authors decided assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg in individuals aged 65 years and over.

The analysis pooled together data from the STEP 1, 3, 4, 5, 8 and 9 trials (only in people with obesity or overweight, not diabetes, because weight loss in obesity drug trials is always lower in people with diabetes than without – thus results cannot be compared or mixed). It included participants aged ≥65 years with body mass index of at least 30 kg/m², or at least 27 kg/m² and at least 1 obesity-related complication (without diabetes) who were randomised to receive semaglutide 2.4 mg or placebo. All participants received lifestyle intervention and, in STEP 3, intensive behavioural therapy. Endpoints were assessed from baseline to week 68 and included percentage change in body weight; proportion of participants achieving categorical body weight reductions (≥10%, ≥15%, ≥20%); change in waist circumference; proportion of participants achieving waist to height ratio (WHtR) <0.53; shift in BMI category; and changes in cardiometabolic risk factors (glucose parameters, blood pressure, serum lipids and hs-CRP). Adverse events (AEs) were also assessed.

Of the total population in the selected trials (N=4523), 358 participants (8%) were aged 65 years or older and included in the analysis (semaglutide 2.4 mg, n=248; placebo, n=110), with most (90%) being aged 65–74 years (and the others 75 years and over). Across the pooled semaglutide and placebo groups at baseline, mean age was 69 years, bodyweight was 99.0 kg, BMI was 36.6 kg/m² and waist circumference was 115 cm; 72% were female.

At week 68, there was a mean −15.4% change in body weight for semaglutide 2.4 mg vs −5.1% for placebo, and a mean −14.3 cm vs −6.0 cm change in waist circumference, respectively. Proportions of participants achieving body weight reduction thresholds in the semaglutide 2.4 mg vs placebo groups were 66.5% vs 15.5% (at least 10%), 46.8% vs 6.4% (at least 15%) and 28.6% vs 2.7% (at least 20%), respectively.

In the semaglutide 2.4 mg group, 11.3% achieved a WHtR <0.53, compared with 4.5% with placebo. A greater proportion of semaglutide-treated participants improved their BMI category from baseline to week 68 compared with placebo (see Figure full abstract). A BMI of <27 kg/m² (so called healthy weight) was achieved by 27.0% of participants in the semaglutide group vs 5.5% in the placebo group; and the proportion of elderly patients in the overweight and obesity class I, II and III categories all fell in the semaglutide group at week 68 due to the increase in participants who had reached a healthy weight.

For participants achieving both a BMI of 27 or less and a WHtR of <0.53 these values were 10.5% vs 2.7%, respectively. Greater improvements in cardiometabolic risk factors were observed with semaglutide 2.4 mg vs placebo (see Table full abstract), including blood pressure, blood fats, cholesterol and glycated haemoglobin (HbA1c – a measure of blood sugar control used in diagnosis of diabetes).

Proportions of participants experiencing AEs and serious AEs in the semaglutide 2.4 mg vs placebo groups were similar for AEs overall (89.1% vs 84.5%), but higher for semaglutide re: serious AEs - 19.0% vs 12.7%, respectively. Constipation and dizziness rates (known side effects of this class of drug) were higher with semaglutide, while fractures and hypoglycaemia were comparable to placebo, both affecting less than 1% in each group.

https://en.wikipedia.org/wiki/Semaglutide

Semaglutide shows sustained weight loss benefits in older adults

Glutamic Acid Helps Fresh-Cut Potatoes Stay Fresh by Silencing Browning Genes | Newswise

In continuation of my update on Glutamic acid 

The study identified a transcriptional regulatory module, StbZIP53-like2–StERF091, that suppresses the activity of key polyphenol oxidase genes linked to browning. By showing how glutamic acid activates this gene-control system, the work provides a clearer molecular basis for safer anti-browning strategies and may support the future development of quality-preserving treatments for fresh-cut potato products and other minimally processed vegetables.

Fresh-cut potatoes are increasingly popular because they fit modern food habits, but their shelf life is limited by rapid enzymatic browning after cutting. Existing methods to control browning include chemical, physical, and biological approaches, yet each has drawbacks. Some chemicals raise food-safety concerns, while physical treatments may cause off-flavors, and many biological methods are still difficult to commercialize. Earlier work had already shown that glutamic acid could reduce browning in fresh-cut potatoes, but the molecular mechanism remained unclear. That unresolved question made it necessary to investigate how glutamic acid regulates browning-related genes and upstream transcription factors in fresh-cut potato tissue.

A study (DOI:10.48130/ph-0026-0004) published in Plant Hormones on 20 March 2026 by Jingying Shi’s & Zunyang Song’s team, Shandong Agricultural University, demonstrates that glutamic acid-induced StbZIP53-like2 and StERF091 form a cooperative regulatory module that represses StPPO2 and StPPO3, thereby alleviating browning in fresh-cut potatoes.

The team first prepared fresh-cut potato shreds and compared untreated samples with samples immersed in a glutamic acid solution, then stored them at 4 °C and collected tissues across multiple time points. They measured ethylene production, performed RNA-seq and RT-qPCR analyses, and screened for transcription factors whose expression changed under glutamic acid treatment. Among 11 bZIP genes detected, StbZIP53-like2 stood out because its expression was strongly induced by glutamic acid. Subcellular localization assays showed that this protein is localized in the nucleus, consistent with its proposed role as a transcription factor. The researchers then examined whether StbZIP53-like2 directly controlled known browning-associated genes. Dual-luciferase assays showed that it repressed the promoter activity of StPPO3, while EMSA and yeast one-hybrid experiments confirmed direct binding to the C-box motif in the StPPO3 promoter. To identify interacting partners, the team screened a cDNA library and found StERF091, another glutamic acid-induced transcription factor. Yeast two-hybrid, GST pull-down, and co-immunoprecipitation assays together demonstrated that StbZIP53-like2 physically interacts with StERF091 both in vitro and in vivo. Like StbZIP53-like2, StERF091 was also localized in the nucleus. Next, the group tested the function of StERF091 in regulating browning genes. They found that StERF091 repressed the promoter activities of StPPO2 and StPPO3, but not StPPO7. EMSA and yeast one-hybrid assays further showed that StERF091 directly binds the GCC-box motifs in the StPPO2 and StPPO3 promoters. Most importantly, co-expression assays revealed that when StbZIP53-like2 and StERF091 acted together, repression of StPPO2 and StPPO3 became stronger than with either factor alone. This demonstrated that the two proteins form a functional inhibitory module that amplifies the anti-browning response triggered by glutamic acid.

Overall, the study shows that glutamic acid alleviates the browning of fresh-cut potatoes by inducing two transcriptional repressors, StbZIP53-like2 and StERF091, which cooperate to suppress StPPO2 and StPPO3. The findings move beyond a simple observation that glutamic acid works and explain why it works at the molecular level. This insight may help guide future preservation technologies aimed at extending the shelf life, visual quality, and commercial value of fresh-cut produce.

https://en.wikipedia.org/wiki/Glutamic_acid

Glutamic Acid Helps Fresh-Cut Potatoes Stay Fresh by Silencing Browning Genes 

Legumes and soy foods may help reduce hypertension risk

In continuation of my continuation of my update on soy ..

A higher dietary intake of soy and legumes is linked to a lower risk of high blood pressure, finds a pooled data analysis of the available evidence, published in the open access journal BMJ Nutrition Prevention & Health.

And the optimal daily amount may be around 170 g of legumes, which include peas, lentils, chickpeas and beans, and 60 to 80 g of soy foods, examples of which include tofu, soy milk, edamame, tempeh, and miso, the findings indicate.

Legumes and soy foods have been associated with an overall lower risk of cardiovascular disease, but the evidence on their potential for lowering high blood pressure is mixed and needs to be systematically quantified, explain the researchers.

To explore this further, the researchers scoured databases for relevant studies published up to June 2025, and found 10 publications that included data from 12 prospective observational studies.

Five studies were from the USA, 5 from Asia (China, Iran, South Korea and Japan), and 2 were from Europe (France and the UK). Nine studies included both men and women, 2 included only women, and 1 included only men.

The number of study participants ranged from 1152 to 88,475 and the number of cases of high blood pressure ranged from 144 to 35,375.

Pooled data analysis of the study findings showed that higher daily intake of legumes and soy foods was associated with a lower risk of developing high blood pressure.

Compared with those with a low intake of legumes, those with a high intake were 16% less likely to develop high blood pressure. Similarly, those with a high intake of soy foods were 19% less likely to develop the condition than those with a low intake.

When assessing the association between quantity and lower risk, a linear reduction (30%) emerged for legumes up to around 170 g/day, while most of the reduction in risk (28-29%) for soy foods was observed at between 60 and 80 g/day, with no further reduction in risk at higher intake.

One hundred grams of legumes/soy is equivalent to a serving size of about one cup or 5–6 tablespoons of cooked beans, peas, chickpeas, lentils, soybeans or a palm-size serving of tofu, explain the researchers.

Using World Cancer Research Fund evidence grading criteria for evaluating the likelihood of causality, the researchers consider the overall evidence to indicate a probable causal relationship between both legume and soy intake and a reduced risk of high blood pressure.

There are plausible explanations for the findings, they say. Legumes and soy are high in potassium, magnesium, and dietary fiber, all of which are known for their blood pressure lowering properties.

And recent research has suggested that the fermentation of soluble fiber from legumes and soy produces short-chain fatty acids that influence blood vessel dilation, while the isoflavone content of soy also seems to help lower blood pressure, they explain.

The researchers acknowledge various limitations to their findings, including the variability of the studies in the pooled data analysis. This included differences in legume types, levels of intake, preparation methods, dietary contexts, and the definition of high blood pressure.

"Despite these limitations, the findings of this meta-analysis have major public health implications, given the alarming global increase in hypertension prevalence," they point out.

"Current legume consumption across Europe and the UK remains below dietary recommendations, with average intakes of only 8–15 g/day, far below the recommendations of 65 to 100 g/day recommended for overall cardiovascular health," they add.

"Although further large-scale cohorts are needed for confirmation, these findings provide further evidence in support of dietary recommendations to the public to prioritise and integrate legumes and soy foods as healthy protein sources in the diet," they conclude.

"This research strengthens the evidence base for the cardioprotective benefits of plant-based diets. The authors have significantly added to the case for using legumes and soy as primary dietary strategies to mitigate the global burden of hypertension," comments Professor Sumantra Ray, chief scientist and executive director of NNEdPro Global Institute for Food, Nutrition and Health, which co-owns BMJ Nutrition Prevention & Health.

"The strengths of the study lie in its rigorous dose-response analyses, which offer practical dietary targets for use in public health guidelines and clinical practice. But we can't entirely rule out the influence of unmeasured influential factors. And the plateauing of benefits for soy at 60–80 g/day warrants further investigation, as it remains unclear if this reflects a true biological limit or is a byproduct of the smaller number of studies available for analysis."

Legumes and soy foods may help reduce hypertension risk

Nicotinamide Linked to Lower Melanoma Risk Post Skin Cancer

In continuation of my update on Nicotineamide

Nicotinamide supplementation was associated with a decreased risk for melanoma among patients with a history of other skin cancers, according to a retrospective cohort study of more than 33,000 veterans.

The study, which won a first-prize poster award at the American Academy of Dermatology (AAD) 2026 Annual Meeting, “suggests that nicotinamide could potentially be effective for primary prevention of melanoma among patients who have had a prior nonmelanoma skin cancer,” noted Lee Wheless, MD, PhD, one of the senior authors, an assistant professor of dermatology at Vanderbilt University and a staff physician with the Tennessee Valley Healthcare System VA Medical Center, both in Nashville, Tennessee.

The effect of nicotinamide, at a dose of 500 mg twice daily, was statistically significant for invasive, but not in situ, melanoma, and it was consistent in both sun-exposed and sun-protected areas, he told Medscape Medical News.

The retrospective cohort study used data from the Veterans Affairs (VA) Corporate Data Warehouse from January 1, 2007, to December 31, 2024. It included a total of 33,581 patients with one or more prior skin cancers of any type. The cohort was predominantly White and men, with comparable mean ages (77.5 years in the exposed group vs 77.1 years in the unexposed group).

The US Department of VA offers nicotinamide, a vitamin B3 derivative, on formulary. Patients exposed to nicotinamide 500 mg twice daily were propensity score matched to unexposed patients based on “numerous skin cancer risk variables to make sure risks at specific timepoints in the patients’ lives matched up,” explained Wheless.

Baseline matching variables included age, sex, race, age at first skin cancer, number and year(s) of prior skin cancers of any type, number of dermatology visits after baseline, chronic lymphocytic leukemia, solid organ transplantation, exposure to acitretin, and field therapy.

More...

https://en.wikipedia.org/wiki/Nicotinamide

Nicotinamide Linked to Lower Melanoma Risk Post Skin Cancer

Metformin's real power may be in the gut

In continuation of my uodate on metformin 

For decades,physicians and scientists thought metformin, the leading type 2 diabetes medication taken by millions worldwide, mainly targets the liver to suppress glucose production. But a new Northwestern University study in mice has found this "wonder drug" instead focuses primarily on the gut, acting to prevent glucose levels rising in the blood by driving glucose utilization inside cells lining the intestine.

The body relies on glucose as a fast and versatile fuel, but too much glucose can lead to insulin resistance and ultimately damage blood vessels and organs. The study found metformin slows mitochondrial energy production in gut cells, forcing the intestine to metabolize extra sugar.

"Metformin essentially helps the intestine suck the glucose out of the bloodstream, which further highlights that the gut plays a major role in regulating blood sugar levels," said corresponding author Navdeep Chandel, professor of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine.

The study is published in Nature Metabolism.

The study builds off findings from previous work in Chandel's lab, which found metformin lowers blood sugar by blocking a specific part of the cell's energy-making machinery called mitochondrial complex I, a key enzyme in cellular respiration.

The new study furthers that work by pinpointing the specific tissue targeted by metformin. The findings suggest directing drugs or supplements to the gut could be an effective strategy for controlling blood sugar, Chandel said.

Chandel is also the David W. Cugell, MD, Professor of Medicine (Pulmonology and Critical Care), Biochemistry and Molecular Genetics and an investigator with the Chan Zuckerberg Initiative. The study's first author is Zach Sebo, a postdoctoral fellow in the Chandel lab who will soon start his own research group at the University of Kansas School of Medicine.

"Our study suggests that revisiting assumptions about metformin's mechanism may offer a more detailed understanding of how it works," Sebo said.

https://en.wikipedia.org/wiki/Metformin

Metformin's real power may be in the gut

FDA Approves Veppanu (vepdegestrant) for the Treatment of ESR1m, ER+/HER2- Advanced Breast Cancer

Arvinas, Inc. (Nasdaq: ARVN), with its partner Pfizer Inc. (NYSE: PFE), announced  the U.S. Food and Drug Administration (FDA)    approval for Veppanu (vepdegestrant) for the treatment of adults with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. This approval marks the first time the FDA has approved a PROteolysis TArgeting Chimera (PROTAC), a type of heterobifunctional protein degrader therapy.

Veppanu™ is the first-and-only FDA-approved PROTAC, a type of heterobifunctional protein degrader

Approval received in advance of FDA-assigned PDUFA date of June 5, 2026; Arvinas and Pfizer remain on track to announce selection of a third party

Veppanu offers a new therapeutic option in ER+/HER2-, ESR1-mutated advanced or metastatic breast cancer, where treatment resistance remains a major clinical challenge

“Today’s FDA approval is a transformative moment for Arvinas as we achieve our first approved medicine and the first-ever approved PROTAC therapy based on the technology we’ve pioneered since 2013,” said Randy Teel, Ph.D., President and Chief Executive Officer at Arvinas. “This milestone demonstrates that targeted protein degradation can translate into meaningful clinical impact. It also strengthens our confidence in the breadth and versatility of our exciting clinical pipeline across oncology, neurodegenerative, and neuromuscular diseases. We are especially encouraged by receiving FDA approval ahead of the June 5 PDUFA date and together with Pfizer, we are on track to announce selection of a third party to bring this new treatment option to patients as soon as possible.”

“For patients living with ESR1 mutant, ER+/HER2 advanced breast cancer, there have been minimal second-line treatment options once standard therapies are no longer effective,” said Erika Hamilton, M.D., Chief Development Officer, Late Phase, and Director, Breast Cancer Research, Sarah Cannon Research Institute, as well as a principal investigator of the VERITAC-2 trial. “The introduction of a new, targeted treatment is an encouraging development for this community and highlights meaningful innovation in the way this disease is treated. The approval of vepdegestrant gives clinicians another tool in the breast cancer treatment arsenal and brings renewed hope to individuals who need additional options.”

Breast cancer is the most common cancer among women worldwide, with many tumors driven by estrogen receptor signaling. While endocrine therapy remains a cornerstone of metastatic ER+/HER2- breast cancer treatment, up to 40-50% of patients treated with endocrine therapy and a CDK4/6 inhibitor have ESR1 mutations, resulting in endocrine resistance and poor prognosis. These patients often experience rapid disease progression and face limited options after first-line therapy. The FDA approval of Veppanu addresses a significant unmet need, offering a new treatment option for adults with ESR1-mutant, ER+/HER2- advanced breast cancer by targeting a key biological driver of resistance to current therapies.

“The approval of Veppanu is an important milestone for patients, their caregivers, and physicians,” said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. “Veppanu addresses an unmet need for patients with this aggressive form of breast cancer who have progressed on their initial therapy. Today’s approval provides a new oral treatment option that showed improved progression free survival when compared to the current standard of care, fulvestrant, which is administered via an intramuscular injection.”

Veppanu was discovered by Arvinas and jointly developed by Arvinas and Pfizer. FDA approval was granted based on data from VERITAC-2 (NCT05654623), a global, randomized, open-label, pivotal Phase 3 clinical trial evaluating vepdegestrant versus fulvestrant. In the trial, among patients with an ESR1 mutation (n=270), vepdegestrant demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 43% compared to fulvestrant. Median PFS was 5 months (95% CI: 3.7, 7.4) in the vepdegestrant arm and 2.1 months (95% CI: 1.9, 3.5) in the fulvestrant arm (hazard ratio 0.57 [95% CI: 0.42, 0.77]; p-value 0.0001). Overall survival was immature with 16% of deaths in this population at the time of the PFS analysis. The majority of adverse events (AEs) with vepdegestrant were low grade (Grade 1-2) and the most common (≥10%) adverse reactions, including laboratory abnormalities, were decreased white blood cells, increased AST, musculoskeletal pain, fatigue, decreased hemoglobin, decreased neutrophils, increased ALT, increased alkaline phosphatase, nausea, decreased blood potassium, increased bilirubin, decreased appetite, electrocardiogram QT prolonged, decreased platelets, and constipation.

Arvinas and Pfizer intend to jointly identify and select a third-party partner with the capabilities and expertise to maximize the commercial potential of Veppanu. The companies are on track to announce selection of a third party.

Arvinas was originally founded based on pioneering research at Yale University, where Professor Craig Crews, Ph.D., co-authored the first-ever paper on PROTAC protein degraders.

What is Veppanu?

Veppanu is a prescription medicine to treat people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced breast cancer or breast cancer that has spread to other parts of the body (metastatic), and whose disease has progressed after at least one line of endocrine-based therapy.

https://en.wikipedia.org/wiki/Vepdegestrant

FDA Approves Veppanu (vepdegestrant) for the Treatment of ESR1m, ER+/HER2- Advanced Breast Cancer

Cogent Biosciences Announces Submission of New Drug Application for Bezuclastinib in Gastrointestinal Stromal Tumors (GIST)

Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases,  announced the completion of the submission of its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for bezuclastinib in patients with Gastrointestinal Stromal Tumors (GIST) who have received prior treatment with imatinib. Based on the positive results from the PEAK trial, the bezuclastinib NDA was submitted under the FDA’s Real-Time Oncology Review (RTOR) program, which is intended to enable a more streamlined review process. Bezuclastinib was also granted Breakthrough Therapy Designation as a treatment for GIST earlier this year.

• Bezuclastinib NDA submitted under the FDA’s RTOR program based on positive results from Phase 3 PEAK trial; bezuclastinib previously granted Breakthrough Therapy Designation in GIST
• Bezuclastinib combination demonstrated 16.5 month mPFS and 46% ORR in imatinib-resistant GIST patients, dramatically improving upon the current standard of care

“We are excited to complete our PEAK NDA submission which marks a significant step toward bringing a new therapy to patients with second-line GIST,” said Andrew Robbins, President and Chief Executive Officer. “Based on the strength of the PEAK data, we believe the bezuclastinib combination has the potential to meaningfully change the treatment landscape for these patients. We are grateful to the patients, investigators, and study teams who made this possible.”

Pivotal data from PEAK, a global, randomized Phase 3 clinical trial evaluating bezuclastinib in combination with sunitinib vs. sunitinib monotherapy in patients with GIST who have received prior treatment with imatinib, were reported in November 2025. As disclosed in the top-line results, the bezuclastinib combination demonstrated a substantial and highly statistically significant clinical benefit on the primary endpoint of progression free survival (PFS), reducing risk of disease progression or death compared to the current standard of care by 50% (hazard ratio of 0.50, 95% CI: 0.39 – 0.65). mPFS, as assessed by blinded independent central review, was 16.5 months for the bezuclastinib combination vs. 9.2 months for sunitinib monotherapy. Additionally, the bezuclastinib combination demonstrated an unprecedented ORR in imatinib-resistant patients, with 46% of patients treated with the bezuclastinib combination achieving an objective response compared to 26% of patients treated with sunitinib. The bezuclastinib combination was generally well tolerated, and no unique risks were observed with the novel combination when compared to the known safety profile of sunitinib. Data for overall survival remains immature.

At the time of data cutoff, based on the number of ongoing patients receiving treatment on the bezuclastinib combination arm, the estimated mean duration of treatment for the bezuclastinib combination is projected to exceed 19 months.

Cogent plans to present full results from the PEAK trial at a major medical meeting during the first half of 2026. Additionally, Cogent is on track this quarter to initiate a Phase 2 trial investigating the benefit of the bezuclastinib plus sunitinib combination for first-line GIST patients with exon 9 mutations who are naive to, or recently initiated treatment with, imatinib. The NDA submission with bezuclastinib in Advanced Systemic Mastocytosis (AdvSM) also remains on track for the first half of 2026.

Bezuclastinib - Expanded Access Program

Working with the FDA, Cogent has established active Expanded Access Programs (EAPs) for U.S. patients with GIST or SM who meet disease-specific criteria and could benefit from treatment with bezuclastinib or the combination of bezuclastinib and sunitinib. A growing number of sites now offer access to the bezuclastinib EAPs. For more information please visit: https://www.cogentbio.com/bezuclastinib-program-development/#our-expanded-access-policy

Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)

Cogent also announced today that, on March 30, 2026, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grants of “inducement” equity awards to six new employees under the company’s 2020 Inducement Plan with a grant date of March 30, 2026. The awards were approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employees received, in the aggregate, (i) nonqualified options to purchase 21,100 shares of Cogent common stock and (ii) 15,700 restricted stock units (RSUs). Each option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a 4-year vesting schedule with 25% vesting on the 1-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date. The RSUs vest annually in equal installments over 4 years from the grant date, provided such employee remains employed through each such vesting date.

https://en.wikipedia.org/wiki/Bezuclastinib

Cogent Biosciences Announces Submission of New Drug Application for Bezuclastinib in Gastrointestinal Stromal Tumors (GIST)

Nuvalent Announces Submission of New Drug Application to FDA for Neladalkib in TKI Pre-treated Advanced ALK-Positive NSCLC

Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, announced the submission to the U.S. Food and Drug Administration (FDA) of the Company's NDA for neladalkib, an investigational ALK-selective inhibitor, in TKI pre-treated advanced ALK-positive NSCLC.

New Drug Application (NDA) based on data in TKI pre-treated patients from the global ALKOVE-1 Phase 1/2 clinical trial

"The advancement of neladalkib from first clinical trial initiation to NDA submission in less than four years represents a remarkable pace in oncology drug development, underscoring the vigor and urgency our team brought to this program and our deep commitment to the ALK-positive NSCLC community," said Darlene Noci, A.L.M., Chief Development Officer at Nuvalent. "We would like to extend our sincere gratitude to the patients, families and investigators who have made this progress possible, and are committed to working closely with the FDA throughout the NDA review process toward our goal of bringing neladalkib to patients as quickly as possible."

The application is based on data in TKI pre-treated patients with advanced ALK-positive NSCLC treated with neladalkib in the global, registration-directed ALKOVE-1 Phase 1/2 clinical trial. In this population, neladalkib demonstrated encouraging overall activity, including intracranial responses, the ability to address key drivers of disease progression, and a generally well-tolerated safety profile consistent with its ALK-selective, TRK-sparing design. The company plans to share detailed results at a future medical meeting.

Neladalkib has received breakthrough therapy designation from the FDA for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC who have been previously treated with 2 or more ALK tyrosine kinase inhibitors and orphan drug designation for ALK-positive NSCLC.

About Neladalkib

Neladalkib is an investigational, brain-penetrant, ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. Neladalkib is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, neladalkib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. Neladalkib has received breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ALK tyrosine kinase inhibitors and orphan drug designation for ALK-positive NSCLC.

About the ALKOVE-1 Phase 1/2 Clinical Trial

The ALKOVE-1 trial (NCT05384626) is a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive NSCLC and other solid tumors. The completed Phase 1 portion enrolled ALK-positive NSCLC patients who previously received at least one ALK TKI, or patients with other ALK-positive solid tumors who had been previously treated or for whom no satisfactory standard of care exists. The Phase 1 portion of the trial was designed to evaluate the overall safety and tolerability of neladalkib, with additional objectives including determination of the recommended Phase 2 dose (RP2D), characterization of the pharmacokinetic profile, and evaluation of preliminary anti-tumor activity. The global, single arm, open label Phase 2 portion is designed with registrational intent for TKI pre-treated patients with advanced ALK-positive NSCLC. Global enrollment in ALKOVE-1 remains ongoing for adult and adolescent patients with ALK-positive solid tumors outside of NSCLC, and adolescent patients with ALK-positive NSCLC.

Nuvalent Announces Submission of New Drug Application to FDA for Neladalkib in TKI Pre-treated Advanced ALK-Positive NSCLC

Some Improvement Seen in Cognitive Function With Exercise, Ibuprofen in Cancer

In continution of my update on Ibuprofen 

For adults with cancer receiving chemotherapy, an exercise intervention and low-dose ibuprofen improved some domains of cognitive function, according to a study published online April 20 in Cancer.

Michelle C. Janelsins, Ph.D., M.P.H., from the University of Rochester in New York, and colleagues randomly assigned 86 adult participants with cancer receiving chemotherapy and reporting cognitive problems to one of four study arms for six weeks: Exercise for Cancer Patients (EXCAP)-ibuprofen, EXCAP-placebo, ibuprofen only, and placebo only. EXCAP is a home-based, low- to moderate-intensity progressive walking and resistance exercise prescription.

The researchers found that compared with the placebo group, participants in the EXCAP-placebo group had significantly better attention performance on the Trail Making Test (–21.57 seconds). Greater improvements were seen for the ibuprofen-only group versus the placebo group (difference of –11.27 seconds). Improvements on the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) "comments from others" subscale were exhibited by participants in both the EXCAP-ibuprofen and EXCAP-placebo groups compared with the placebo group. Participants in the EXCAP-placebo group had a significant improvement on Rapid Visual Processing mean latency compared with the placebo group; those receiving ibuprofen had an improvement compared with those receiving placebo, which was attributed to a trend after adjustment for reading score. Compared with those not receiving ibuprofen, the ibuprofen group performed less well on the Hopkins Verbal Learning Test‐Revised delayed.

"We are encouraged by the findings of this trial that suggest possible benefits of both interventions for some cognitive domains. Clearly, we saw a more pronounced effect with exercise, which is notable considering the multiple health benefits of exercise for cancer survivors," Janelsins said in a statement.

https://en.wikipedia.org/wiki/Ibuprofen

Some Improvement Seen in Cognitive Function With Exercise, Ibuprofen in Cancer - Drugs.com MedNews

Combining Cannabinoid With Opioid Does Not Relieve Pain in Knee Osteoarthritis

For patients with knee osteoarthritis, combining a cannabinoid medication with an opioid does not provide additional pain relief, according to a study published in the May issue of Anesthesiology.

Katrina R. Hamilton, Ph.D., from Johns Hopkins University School of Medicine in Baltimore, and colleagues examined the acute analgesic and drug effects of synthetic delta-9-tetrahydrocannabinol and hydromorphone, alone and in combination, in 21 individuals with knee osteoarthritis (mean age, 63.4 years). Participants received oral combinations of placebo, hydromorphone (2 mg), and dronabinol (10 mg).

The researchers found greater pressure pain threshold analgesia for hydromorphone than dronabinol and greater capsaicin and noncapsaicin sensitized mechanical temporal summation analgesia versus placebo. No significant drug-related differences were seen for clinical pain severity, thermal threshold or tolerance, temporal summation, cold pressor, conditioned pain modulation, capsaicin-induced thermal threshold, central sensitization, general pain sensitivity, or physical functioning (two-minute walking distance, Timed Up and Go, and total stair climb time). Compared with all conditions, hydromorphone impaired working memory accuracy and produced greater good effects than placebo in terms of secondary outcomes. Working memory reaction time was impaired with hydromorphone + dronabinol, which produced greater high ratings than placebo, greater drug effects than placebo + hydromorphone, and higher nausea than hydromorphone. Greater high ratings were seen for dronabinol than hydromorphone.

"Some patients believe combining cannabis with opioids can help with pain, and clinicians may recommend or prescribe it in states where cannabis is legal," Hamilton said in a statement. "Our study suggests that isn't the case and patients may experience more side effects when the drugs are combined."

https://en.wikipedia.org/wiki/Cannabinoid

https://en.wikipedia.org/wiki/Opioid

Combining Cannabinoid With Opioid Does Not Relieve Pain in Knee Osteoarthritis - Drugs.com MedNews

FDA Approves Idvynso (doravirine and islatravir) for the Treatment of HIV-1 Infection in Adults

In continuation of my update on Doravirine

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced the U.S. Food and Drug Administration (FDA) approval of  Idvynso, a new, two-drug single-tablet regimen of 100 mg doravirine and 0.25 mg islatravir, for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine. Idvynso is contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers and lamivudine (3TC) or emtricitabine (FTC). Co-administration with these drugs may decrease the effectiveness of Idvynso. See additional selected safety information on the following pages. Idvynso (pronounced ihd-VIHN-soh) will be available in pharmacies after May 11.

                                                                Islatravir

Doravirine

• Idvynso is approved for adults with virologically suppressed HIV-1 with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine
• Idvynso is the first and only non-INSTI, tenofovir-free, once-daily, complete two-drug regimen to demonstrate non-inferior efficacy in a head-to-head Phase 3 trial versus three-drug regimen Biktarvyi (BIC/FTC/TAF)

“Advances in HIV treatment mean more people living with HIV are living longer — a remarkable achievement,” said Carl Baloney, Jr., president and chief executive officer of AIDS United. “People aging with HIV face additional health challenges, including managing multiple chronic conditions and medications at the same time. It is essential that management of HIV considers these factors in addition to virologic suppression when choosing an HIV treatment regimen.”

“Idvynso combines islatravir, a next-generation NRTI with multiple mechanisms of action, including translocation inhibition, with doravirine, an NNRTI with an established efficacy and safety profile. As the only two-drug, non-INSTI, tenofovir-free regimen, Idvynso expands therapeutic diversity beyond the currently available oral treatment options,” said Dr. Eliav Barr, senior vice president and chief medical officer, Merck Research Laboratories. “As the health needs of adults living with HIV change over time, Idvynso gives clinicians a new choice for HIV treatment. This approval marks an important new chapter in Merck’s long-standing commitment to research and discovery for people living with HIV.”

Idvynso is a complete regimen; co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. Severe skin reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis, have been reported with doravirine-containing regimens. Drug Rash with Eosinophilia and Systemic Symptoms was reported with Idvynso. Concomitant use of Idvynso and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of Idvynso and possible development of resistance, or possible clinically significant adverse reactions from greater exposures of a component of Idvynso. See additional selected safety information on the following pages.

“Idvynso is the first non-INSTI, tenofovir-free, two-drug regimen to demonstrate non-inferior efficacy to standard oral antiretroviral regimens, including Biktarvy. This makes Idvynso a potential alternative for people with virologically suppressed HIV who may need to switch their treatment,” said Dr. Amy Colson, director of research at Community Resource Initiative, Boston, Massachusetts.

Phase 3 studies supporting approval of Idvynso

The efficacy and safety of Idvynso is supported by Week 48 data from two randomized, active-controlled, non-inferiority trials [Trial 052 (NCT05630755) and Trial 051 (NCT05631093)] in virologically-suppressed (HIV-1 RNA less than 50 copies per mL) adults living with HIV. Participants must have been stably suppressed on their baseline regimen for at least 3 months prior to trial entry and had no history of treatment failure. Across the two trials, a total of 708 participants received once-daily Idvynso; of these, 81 (11%) participants were aged 65 years and older, including 10 (1%) aged 75 years and older.

In the double-blind Trial 052, participants were switched from Biktarvy [bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)] to Idvynso. A total of 513 participants were randomized (2:1) and were switched to once-daily Idvynso (n=342) or remained on BIC/FTC/TAF (n=171). At baseline, participants had a mean age of 48 years (range: 19 to 77), 21% of participants were female, 61% were White, 31% were Black/African American, and 6% were Asian. A total of 23% identified as Hispanic/Latino.

In the open-label Trial 051, participants were switched from an oral ART (antiretroviral therapy) regimen to Idvynso. A total of 551 participants were randomized (2:1) and were switched to once-daily Idvynso (n=366) or remained on their baseline ART (bART) (n=185). Randomization was stratified by bART. At baseline, participants had a mean age of 50 years (range: 18 to 83), 40% of participants were female, 39% were White, 45% were Black/African American, and 5% were Asian. A total of 15% identified as Hispanic/Latino. At enrollment, 64% of the participants were receiving integrase strand transfer inhibitor (INSTI)-based regimens, 5% protease inhibitor (PI)-based regimens (including combinations with INSTI), and 30% were receiving other regimens.

https://en.wikipedia.org/wiki/Islatravir

https://en.wikipedia.org/wiki/Doravirine

FDA Approves Idvynso (doravirine and islatravir) for the Treatment of HIV-1 Infection in Adults

Injectable peptides are the new anti‑aging trend. But what evidence do we have they're safe for humans?

Injectable peptides are the new anti-aging trend sweeping the beauty industry. These compounds are promoted on social media as tools for skin repair, collagen production and "cellular rejuvenation." They are widely available online from overseas sellers, despite many peptides being unregulated in Australia.

But what's in them? And are they safe?

Earlier this year, three people in the United States were fined thousands of dollars for their role in providing peptide injections, at an anti-aging festival in Las Vegas, to two women who later became critically ill. The pharmacy board was unable to determine why they got sick, and what precisely the serums contained.

Our work with colleagues at Steroid QNECT, a hotline where people can seek confidential advice about enhancement drugs, shows that people are already injecting peptides in Australia.

But regulation is not keeping up. And there are still major gaps in the evidence about whether peptides' anti-aging claims stack up, and whether they are safe for humans.

What are injectable peptides, and why are they trending?

Peptides are short chains of amino acids—the building blocks of proteins. They act as chemical messengers in the body and play a key role in many processes. These include helping repair skin and calming inflammation.

The body naturally produces peptides. Synthetic peptides are manufactured to mimic or enhance these natural functions.

Certain peptides have clear medical uses. For example, glucagon-like peptide-1 (GLP-1) drugs, such as semaglutide, are approved for diabetes and weight management—sold as Ozempic and Wegovy. This is based on strong clinical trial evidence that they are effective.

But a growing number of peptides are being marketed for cosmetic and anti-aging purposes, without approval from Australia's therapeutic goods regulator.

Peptides such as GHK-Cu, BPC-157 and TB-500 are sold online with claims they can enhance collagen production, accelerate skin repair, reduce wrinkles, and even reverse aspects of biological aging.

TB 500

BPC-157

GHK-Cu

https://en.wikipedia.org/wiki/TB-500

https://en.wikipedia.org/wiki/BPC-157

https://en.wikipedia.org/wiki/Copper_peptide_GHK-Cu

Experimental drug cuts Parkinson's-linked protein up to 60% in early trial

An experimental drug designed to silence a gene strongly linked to Parkinson's disease has shown encouraging effects in a first-in-human clinical trial, according to a study published in Nature Medicine. The drug, known as   BIIB094 (ION859), an antisense oligonucleotide targets LRRK2, the most common genetic contributor to Parkinson's disease; variants in LRRK2 are known to increase the risk of developing the neurodegenerative disorder, which affects nearly 10 million people worldwide

Scientists have long believed that lowering the activity of the LRRK2 protein could help slow or modify the disease, but turning that idea into a viable therapy has remained a challenge, said co-author of the study Danielle Larson, MD, '15, '18 GME, assistant professor in the Ken & Ruth Davee Department of Neurology's Division of Movement Disorders.

"This was a multicenter clinical trial looking at an antisense oligonucleotide therapy for LRRK2-specific Parkinson's disease," Larson said. "The main goal was to examine the safety of delivering this therapy to patients, with the hope that if it proved safe, future studies could evaluate whether it might slow disease progression."

The study tested whether BIIB094 could safely reduce LRRK2 levels in people with Parkinson's disease. The results suggest it can be done without serious safety concerns, Larson said.

In the randomized, placebo-controlled trial, 82 participants with Parkinson's disease were enrolled across two study segments. In the first, 40 participants received a single dose of BIIB094 or placebo. In the second, 42 participants received four doses of the drug or placebo, administered every four weeks. The therapy was delivered intrathecally: directly into the cerebrospinal fluid through a lumbar puncture.

Participants in the second section were stratified based on whether they carried a known LRRK2 genetic variant.

Across both parts of the trial, the treatment was generally well tolerated. While adverse events were common, they were mostly mild to moderate and did not limit dosing. No serious adverse events related to BIIB094 were reported, according to the study.

Beyond safety, the study provided strong evidence that BIIB094 hit its intended biological target. Analysis of cerebrospinal fluid showed that levels of LRRK2 protein fell by as much as 59% in treated participants.

These reductions were observed regardless of whether patients carried a known LRRK2 mutation, suggesting the therapy could potentially affect a broader group of Parkinson's patients, not just those with a genetic diagnosis, Larson said.

"The antisense oligonucleotide was designed specifically to reduce LRRK2 expression," Larson said. "Because overactivity of this protein kinase is thought to be part of the problem in Parkinson's disease, reducing LRRK2 levels could be protective and potentially modify the disease."

The new findings hint at a possible mechanism by which LRRK2-targeting therapies could influence the underlying disease process, rather than simply addressing symptoms, Larson said.

However, Larson cautioned that the trial was not designed to assess clinical benefits such as changes in movement, cognition, or disease progression. Larger and longer studies will be needed to determine whether reducing LRRK2 levels translates into meaningful improvements for patients.

"The next step would be a phase 2 study with a larger group of patients," Larson said. "Instead of focusing only on safety, those trials would look at efficacy, whether the therapy can slow disease progression using motor assessments and standard Parkinson's rating scales."

The findings mark an important step toward targeted treatments that address the root biology of Parkinson's disease and underscore the potential of BIIB094 and other precision-medicine approaches, Larson said.

"This is one of the first antisense oligonucleotide, or ASO, therapies in Parkinson's disease to have safety and tolerability data," Larson said. "It really paves the way for other ASO-based treatments to be developed, potentially targeting different biological pathways."

https://www.nature.com/articles/s41591-026-04262-4

Experimental drug cuts Parkinson's-linked protein up to 60% in early trial